Wnt signaling is one of the key signaling pathways that governs many aspects of normal development including limb development, body axis extension, CNS development and kidney development by controlling cell proliferation, differentiation and migration (Berger, W., et al. (1992) Nat Genet 1:199-203; Chen, Z. Y., et al. (1992) Nat Genet 1:204-208; Willert, K., et al. (2003) Nature 423:448-452; Semenov, M. V., et al. (2001) Curr Biol 11:951-961). Wnt signaling is also known to play important roles in homeostasis of adult tissue. For example, deregulation of Wnt signaling, usually an aberrant activation, is highly associated with several forms of cancer in humans (Polakis, P. (2000) Genes Dev 14:1837-1851; He, X., et al. (2004) Development 131:1663-1677). More recently, Wnt signaling has been implicated in maintaining the self-renewal capacity of embryonic and hematopoietic stem cells, or inducing neural fate differentiation of neural stem cells (Kuhl, M. (2004) Front Biosci 9:967-974; Xu, Q., et al. (2004) Cell 116:883-895; Inoue, T., et al. (2004) Cell 118:795-806, Yoon, J. K., and Wold, B. (2000) Genes Dev 14:3204-3214). Over the last two decades since the first Wnt ligand was identified (Yoon, J. K., Moon, R. T., and Wold, B. (2000) Dev Biol 222:376-391; Kamata, T., et al. (2004) Biochim Biophys Acta 1676:51-62), significant progress has been made in identifying key signaling components including the receptors, and determining their roles in the Wnt signaling pathway (Kazanskaya, O., et al. (2004) Dev Cell 7, 525-534; Adams, J. C., and Tucker, R. P. (2000) Dev Dyn 218:280-299; Fernig, D. G., and Gallagher, J. T. (1994) Prog Growth Factor Res 5:353-377; Takada, S., et al. (1994) Genes Dev 8:174-189). Numerous studies suggest that Wnt signaling is regulated at various levels of the signaling axis either positively or negatively and a sum of positive and negative regulation determines the strength and activity of Wnt signaling at a given time and location in a certain biological system. Therefore, identifying these regulators and elucidating their regulatory mechanisms that affect Wnt signaling is of critical importance to this field. Better understanding of these regulators is worthwhile considering the potential impact on the design and development of diagnostic and/or therapeutic tools for the diseases associated with Wnt signaling in humans.
Therefore, what is needed are both nucleotide sequences and the encoded proteins that can be used to 1) better understand the biochemistry involved in the regulation of such critical physiological pathways and, 2) for the treatment of disease states that result from the misregulation of the Wnt signaling pathway.